Phase-transfer catalysis is a technique for facilitating reactions between aqueous and organic phase reactants that normally do not proceed rapidly because neither reactant is soluble in the phase containing the other reactant. Often, the aqueous phase reactant is insoluble in the organic phase.
Typically, in phase transfer catalysis a phase transfer agent is added to a two-phase mixture to extract an aqueous-phase reactant into the organic phase so that a reaction can proceed. This technique has been exploited routinely by chemists for about ten to fifteen years as a tool for laboratory synthesis and, recently, the advantages of phase-transfer catalysts for industrial-scale production have been recognized. As a result, phase-transfer catalysis is now employed in the manufacture of many agricultural chemicals, pharmaceuticals, and other specialty chemicals and intermediates.
Phase-transfer catalysis may also be used where one of the coreactants has low water solubility. Often, phase-transfer catalysis will be used in reactions that occur in an organic media where two or more reactants are involved and all but one of these is soluble in the organic phase. The one insoluble reactant is usually an anion dissolved in an aqueous phase. In the absence of the phase transfer catalyst (otherwise known as "PTC"), the solubility of the anion in the organic phase is generally so small that negligible reaction rates are observed. However, the presence of a PTC in the reaction mixture promotes the transfer of the reacting anion into the organic phase, thus allowing the reaction to proceed at a significantly higher rate. Such organic reactants frequently will be structurally complex and are costly to manufacture. As an example, a number of the pyrethroid alpha-cyano esters are prepared by a phase-transfer-catalyzed coupling reaction between a substituted benzaldehyde moiety and a water-soluble cyanide salt, accompanied by reaction of the cyanohydrin so produced with a chrysanthemic acid derivative (typically an acyl halide). Baum, U.S. Pat. Nos. 4,254,050; 4,254,051; and 4,254,052.
Examples of general reaction classes amenable to phase transfer catalysis include nucleophilic substitution reactions, carbene formation, alkylations and alkoxylations, oxidations and reductions, and condensation, elimination, and addition reactions. More specifically, phase transfer catalysis can be used to catalyze the formation of ring compounds from straight-chain halocarbons, esters from acids, and ethers from alcohols; the synthesis of alkylchlorides and other alkyl halides by anion displacement; the alkylation of carbanions; and the oxidation of olefins to carboxylic acids. Freedman, H. H. (Pure and Appl Chem., 58 (1986) 857-868) sets forth a compilation of reaction types and industrial applications of phase transfer catalysis.
Conventionally, phase transfer catalysis is conducted in dispersed-phase systems wherein a two-phase mixture containing a phase transfer catalyst or PTC is stirred vigorously in a tank or other vessel to form an agitated interface or a dispersion (FIG. 3). Typically, the overall rate of conversion initially increases with stirring speed, since increasing the stirring speed causes the formation of greater numbers of smaller drops with higher interfacial areas. Ultimately, however, the conversion rate plateaus with increased stirring speed, as the heterogeneous reaction system undergoes a transition from mass-transfer control to bulk organic-phase kinetic control.
Unfortunately, a number of problems are associated with the small drop sizes required to maximize phase transfer catalysis reaction rates. In particular, some PTCs are surface-active by their very nature and act as effective emulsification agents. This is an advantage where dispersion and the creation of high interfacial areas are the objectives, but a disadvantage when it comes time for the phases to coalesce and be separated from one another. In addition to the practical difficulties associated with the continual making and breaking of dispersions and emulsions, and recovery of products therefrom, incomplete phase separation and entrainment of one phase into the other can result in loss of expensive product and phase transfer agent or PTC, as well as reduced product purity.
Other disadvantages of conducting phase transfer catalysis in dispersed-phase systems is its irreproducibility and relative inflexibility. For example, in conventional phase transfer catalysis, one is constrained to operate over relatively narrow ranges of volumetric phase ratios, and the relative mass transfer resistances of the aqueous and organic boundary layers cannot be readily and independently controlled. Scale-up of biphasic systems is often unreliable as well. With conventional dispersed-phase PTC processing there is relatively little way of independently manipulating boundary layer to bulk phase volume ratios, interfacial area to bulk phase volume ratios, and absolute and relative aqueous-phase and organic-phase mass transfer resistances in order to improve the efficiency of phase transfer catalysis.
Phase transfer catalysis has also been carried out with the use of ion exchange membranes serving as partitions in electrochemical diaphragm cells. U.S. Pat. No. 4,414,079 to Yamataka et al. and 4,277,318 to Matlock et al. Phase Transfer Catalysts have been covalently attached to capsule membranes which separate an aqueous phase outside of the capsule from an organic phase inside of the capsule. Once these capsules are formed, however, there is no way to provide fresh organic phase material to the inner portion of the capsule or continuously remove any product or reactant from that phase. Okahata et al., J. Chem. Soc., Chem. Comm., No. 13, pp. 920-922 (1985).
The different phases of biphasic (i.e. aqueous/organic) systems have been separated with membranes, for instance, in the conduct of solvent extraction operations. (FIG. 4) U.S. Pat. Nos. 3,956,112 to Lee et al. and 3,957,504 to Ho et al. However, catalysis reactions are not disclosed as taking place during membrane solvent extractions.
Therefore, it is an object of the present invention to provide a method for carrying out phase transfer catalysis without the problems associated with mixing of dispersed phase systems and phase transfer catalysts.
It is a further object of this invention to enhance the separability of the phase components and reaction products after phase transfer catalysis.
It is an additional object of this invention to provide reliable, reproducible and controllable phase transfer catalysis which is capable of meeting the requirements of high-level industrial production.